Biochemistry of Coagulation - Goueli

Question 1

What does Aspirin inhibit?

Answer 1

• Primary Hemostasis
  
  • irreversibly inhibits COX-1 from generating Thromboxane A₂
  • Low-dose aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation during the lifetime of the affected platelet (8–9 days)

Question 2

What does the von Willebrand Factor (vWF) do?

Answer 2

• mediates the adhesion of platelets to the collagen exposed on endothelial cell surfaces
• acts as a bridge between GP Ib-GP V-GP IX complex on the surface of platelets and collagen fibrils
• also binds to and stabilizes coagulation factor VIII

Question 3

What is the MOA of Warfarin (Coumadin)?

Answer 3

• Slow and long acting blood anticoagulant with a structure resembling that of Vitamin K
• Similar structure allows the compound to compete with Vitamin K
  
  • blocks the vitK reductase enzymes used to regenerative active vitK
    
    • Prevent gamma-carboxylation of glutamate residues in factors II, VII, IX, X, and proteins C and S
    • factors consequently cannot bind calcium and thus cannot bind to their phospholipid membrane sites of activation

Question 4

What is the primary reason a physician must “bridge with heparin” when starting a patient on Warfarin (Coumadin)?

Answer 4

• Warfarin (Coumadin) also blocks the activity of proteins S and C
  
  • loss of anticoagulant factors leads to increased risk of clotting initially

Question 5

What is the MOA of Heparin?

Answer 5

• Binds to and activates Antithrombin III
  
  • leads to thrombin inactivation
  • also blocks the activity of factors:
    
    • VIIIa
    • IXa
    • Xa
    • XIa

Question 6

What is the difference between HMW Heparin and LMW? When do you give each?

Answer 6

• HMW heparin
  
  • binds to plasma proteins and cell surfaces in addition to its primary target (ATIII)
  • use for loading dose
• LMW heparin
  
  • fewer nonspecific interactions than HMW
  • effects are easier to predict
  • constant monitoring isn’t reguired
  • use for short-term or long-term use